Persistent skewing of the T-cell profile in adolescents adopted internationally from institutional care

Brie M. Reid, Christopher L. Coe, Colleen M. Doyle, Dagna Sheerar, Alla Slukvina, Bonny Donzella, Megan R. Gunnar

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The developing immune system is an adaptive system, primed by antigens, responsive to infectious pathogens, and can be affected by other aspects of the early rearing environment, including deviations from the normal provision of parental care. We investigated whether early rearing in an institutional setting, even when followed by years living in supportive and well-resourced families, would be associated with a persistent shift in T cell profiles. Immunophenotyping was used to enumerate CD4+ CD57+ and CD8+ CD57+ subsets, with gating strategies employed to differentiate naïve, central-memory, effector-memory, and terminally differentiated EM cells expressing CD45RA (TEMRA). Blood samples were collected from 96 adolescents, and PBMC isolated via Ficol gradient, followed by an optimized immunophenotypic characterization. CMV antibody titers were determined via ELISA. Adopted adolescents had lower CD4/CD8 ratios than did the control adolescents. Early rearing had a significant effect on the T cells, especially the CD8+ CD57+ CM, EM, and TEMRA cells and the CD4+ CD57+ EM cells. Adolescents who had spent their infancy in institutions before adoption were more likely to be seropositive for CMV, with higher antibody titers. CMV antibody titers were significantly correlated with the percentages of all CD8+ CD57+ cell subsets. In the statistical modeling, CMV antibody titer also completely mediated the relationship between institutional exposure and the ratio of CD4-to-CD8 cells, as well as the percentages of CD4+ CD57+ and CD8+ CD57+ subsets. These findings demonstrate that persistent immune differences are still evident even years after adoption by supportive American families. The shift in the T cells was associated with being a latent carrier of CMV and may reflect the role of specific T cell subsets in Herpes virus containment. In older adults, sustained CMV antigen persistence and immunoregulatory containment ultimately contributes to an accumulation of differentiated T cells with a decreased proliferative capacity and to immune senescence.

Original languageEnglish (US)
Pages (from-to)168-177
Number of pages10
JournalBrain, Behavior, and Immunity
Volume77
DOIs
StatePublished - Mar 2019

Bibliographical note

Funding Information:
We would like to express our gratitude to the families who make this research possible. Thanks are also due to the recruiting and collection team: Lea Neumann, Heather Taylor, Tori Simenec, Aurora Wiseman, Melissa Engel, and Anna Parenteau, and the phlebotomy team at the UM Clinical and Translational Science Institute. This research was supported by a grant from the National Institute of Child Health and Human Development [R21 HD086312] to MRG and CLC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional support for the immunophenotyping was provided by the Special BD LSR Fortessa Shared Instrumentation Grant 1S100OD018202-01 and the University of Wisconsin Carbone Cancer Center Support Grant P30 CA014520. This material is based upon work also supported by the National Science Foundation Graduate Research Fellowship (NSF Grant No. 00039202, awarded to BMR and NSF Grant No. 2016199960, awarded to CMD). All opinion, findings, conclusions or recommendations expressed are those of the authors and do not necessarily reflect the views of the NSF.

Funding Information:
We would like to express our gratitude to the families who make this research possible. Thanks are also due to the recruiting and collection team: Lea Neumann, Heather Taylor, Tori Simenec, Aurora Wiseman, Melissa Engel, and Anna Parenteau, and the phlebotomy team at the UM Clinical and Translational Science Institute. This research was supported by a grant from the National Institute of Child Health and Human Development [R21 HD086312 ] to MRG and CLC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional support for the immunophenotyping was provided by the Special BD LSR Fortessa Shared Instrumentation Grant 1S100OD018202-01 and the University of Wisconsin Carbone Cancer Center Support Grant P30 CA014520 . This material is based upon work also supported by the National Science Foundation Graduate Research Fellowship ( NSF Grant No. 00039202 , awarded to BMR and NSF Grant No. 2016199960, awarded to CMD). All opinion, findings, conclusions or recommendations expressed are those of the authors and do not necessarily reflect the views of the NSF.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • Adolescence
  • Adoption
  • CD4/CD8
  • CD57
  • Cytomegalovirus
  • Early adversity
  • Herpes virus
  • Institutional care
  • T cells
  • TEMRA

PubMed: MeSH publication types

  • Journal Article
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

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